Prognosis in clinical cancer is an area of great concern and interest. It is important to know the aggressiveness of the malignant cells and the likelihood of tumor recurrence or spread in order to plan the most effective therapy. Breast cancer, for example, is managed by several alternative strategies. One of every nine women currently develops breast cancer at some point in her life. In some cases local-regional therapy is utilized, consisting of mastectomy or lumpectomy with or without radiation, while in other cases when spread of disease is detected or suspected, systemic therapy is instituted, such as chemotherapy or hormonal therapy. Among women with early-stage breast cancers treated with lumpectomy and local radiotherapy, 10-20% will experience local recurrences and 30-40% will develop distant metastatic disease which is often fatal (Fischer et al. 1991, Lancet 338:327-331).
Current treatment decisions for individual breast cancer patients are frequently based on (1) the number of axillary lymph nodes involved with disease, (2) estrogen receptor and progesterone receptor status, (3) the size of the primary tumor, and (4) stage of disease at diagnosis. It has also been reported that DNA aneuploidy and proliferative rate (percent S-phase) can help in predicting the course of disease. In addition, the overexpression of the HER2/Neu oncoprotein has been shown to predict breast cancer patients at risk for metastatic disease and novel therapeutic strategies have been developed to target this receptor (Slamon et al. U.S. Pat. No. 4,968,603; Slamon et al. 1989, Science 244:707-712). However, even with these additional factors, practitioners are still unable to accurately predict the course of disease for all breast cancer patients. There is clearly a need to identify new markers, in order to separate patients with good prognosis who may not require further therapy from those more likely to recur who might benefit from more intensive treatments.
This is particularly true in the case of breast cancer which has not progressed to the axillary lymph nodes. There is now evidence in prospective randomized clinical trials that adjuvant endocrine therapy and adjuvant chemotherapy beginning immediately after surgical removal of the primary breast tumor can be of benefit in some of these node-negative patients. This has led to official and unofficial recommendations that most if not all node-negative breast cancer patients should be considered for some form of adjuvant therapy. But since the majority (about 70%) of these patients enjoy long-term survival following surgery and/or radiotherapy without further treatment, it may be inappropriate to recommend adjuvant therapy for all of these patients. Accordingly, there is a need for methods to distinguish those node-negative patients who are “cured” from those destined to recur, such that only the latter are treated. Thus, there is a great need for a general method of predicting tumor recurrence or spread in these patients and in cancer patients in general once a primary tumor is detected. The present invention satisfies these needs and provides related advantages as well.